RESUMO
The long non-coding RNA MALAT-1 plays an important role in cancer prognosis. The present research aimed to elucidate its precise predictive value in various human carcinomas. A quantitative meta-analysis was performed by searching PubMed, Embase, Web of Science, and Cochrane Library (most recently, January 2015) databases, and extracting data from studies that investigated the association between MALAT-1 expression and survival outcomes in patients of various cancers. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated as a measure of generalized effect. This meta-analysis included 1317 cases from 12 datasets. Our investigation revealed that poor overall survival (OS; HR = 2.14, 95% CI = 1.74-2.64) and shortened disease-free, recurrence-free, disease-specific, or progression-free survival (HR = 2.13, 95% CI = 1.22-3.72) can be predicted by high MALAT-1 expression for various cancers. Moreover, elevated MALAT-1 levels significantly correlated with decreased OS in a renal cell carcinoma (RCC) subgroup (HR = 3.43, 95% CI = 1.80-6.53). These results imply that MALAT-1 can be used to predict unfavorable prognoses for several cancers, particularly RCC.
Assuntos
Carcinoma/genética , Regulação Neoplásica da Expressão Gênica , RNA Longo não Codificante/genética , Adulto , Idoso , Biomarcadores Tumorais , Carcinoma/diagnóstico , Carcinoma/terapia , Intervalo Livre de Doença , Humanos , Pessoa de Meia-IdadeRESUMO
This study aimed to investigate the properties of mutations of the active efflux pump genes acrA/B and tolC in Escherichia coli CVCC 1547 when induced by different drugs. The mutations were isolated in vitro by exposing E. coli CVCC 1547 to stepwise increases in the concentration of ceftriaxone (CRO), amikacin (AMK), or ciprofloxacin. The results showed that the minimum inhibitory concentrations for the corresponding drugs increased, as did the minimum inhibitory concentrations for other fluoroquinolones and ß-lactam drugs that were not inducers. DNA sequence analyses of the acrA/B and tolC genes of the mutants and comparison with the parent strain revealed that genetic variations had occurred. Three point mutations resulted in amino acid changes in the proteins expressed. Specifically, strain CRO10 had a mutation in acrA, A309G, that resulted in a Thr-103 to Ala substitution, and a mutation in tolC, G735A, that changed Ala-245 to Thr; strain AMK20 (and AMK30) had a Val-447 to Ile amino acid change in acrB. In addition to the missense mutations in these strains, we detected 7, 20, and 15 nonsense mutations in acrA, acrB, and tolC, respectively. To sum up, multiple genetic sequence variations and some changes in amino acid sequences were detected when E. coli CVCC 1547 was challenged in vitro with CRO, AMK, or ciprofloxacin. These changes may have given rise to multidrug-resistant strains.
Assuntos
Proteínas da Membrana Bacteriana Externa/genética , Farmacorresistência Bacteriana Múltipla/genética , Proteínas de Escherichia coli/genética , Lipoproteínas/genética , Proteínas de Membrana Transportadoras/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Amicacina/farmacologia , Ceftriaxona/farmacologia , Ciprofloxacina/farmacologia , Códon sem Sentido/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Regulação Bacteriana da Expressão Gênica , Mutação de Sentido Incorreto/efeitos dos fármacos , Análise de Sequência de DNARESUMO
Extended-spectrum ß-lactamases (ESBLs) and AmpC ß-lactamases produced by a clinical isolate of Klebsiella pneumoniae from chickens were detected with confirmatory phenotypic tests of the Clinical and Laboratory Standards Institute. The minimum inhibitory concentrations of 18 antibacterial drugs against K. pneumoniae were determined by the 2-fold microdilution method. The genotype and subtype of the ESBL-producing and AmpC ß-lactamase-producing K. pneumoniae isolate were identified by PCR amplification of the enzyme-encoding genes followed by DNA sequencing analysis. K. pneumoniae K(1) isolate was an ESBL-producing and AmpC ß-lactamase-producing bacteria with high resistance to ß-lactam antibiotics, such as penicillins, third-generation cephalosporins, fluoroquinolones, and aminoglycosides. The sequence analysis showed that K. pneumoniae K(1) harbored TEM-type, SHV-type, CTX-M-type, and ACT-type AmpC ß-lactamase nucleotide sequences. The TEM-type sequence was designated as TEM-1; the SHV-type sequence was designated as SHV-11; the CTX-M-type sequence was designated as CTX-M-14. Compared with the ACT-like sequence (EF078894), the ACT-type sequence was characterized by 8 nucleotide mutations (A(75)G, C(84)G, T(90)C, A(105)G, G(213)A, G(246)A, C(309)T, and T(315)C). Only one mutation at position 75 led to an amino acid substitution (Asn28Lys). The bla(ACT) type was an ACT-like derivative.